title: Immune-regulatory transcriptional responses in multiple organs of Atlantic salmon after tributyltin exposure, alone or in combination with forskolin.
abstract: Tributyltin (TBT) is a widespread marine pollutant that influences physiological conditions of fish and other aquatic organisms. In addition to effects on reproduction, the immune system has been proposed as a possible target for TBT effects. In the present study, the effects of TBT exposure were examined on the expression of genes involved in immune system compentence in liver and head kidney of Atlantic salmon, in the presence and absence of a second-messenger activator (forskolin). Juvenile salmon were force-fed a diet containing TBT (0-solvent control, 0.1, 1, or 10 mg/kg fish) for 72 h. Consequently, fish from the control group and 10-mg/kg TBT group were exposed to the adenylate cyclase (AC) activator forskolin (200 μg/L) for 2 or 4 h. Forskolin was selected for this study because it is known to exhibit potent immune system enhancement by activating macrophages and lymphocytes. After sacrifice, liver and head kidney were sampled and transcript changes for interleukin (IL)-1β, IL-10, transforming growth factor (TGF) β, interferon (INF) α, INFγ, tumor necrosis factor (TNF) α, Mx3, and insulin-like growth factor (IGF)-1 were determined in both tissues by quantitative polymerase chain reaction (qPCR) using gene-specific primers. TBT, when given alone and also in combination with forskolin, decreased IL-1β, TNFα, IFNγ, IFNα, Mx3, and IGF-1 gene expression. In contrast, IL-10 and TGFβ transcripts were increased after TBT exposure alone and also in combination with forskolin. Generally, these effects were largely dependent on TBT dose and time of exposure when given in combination with forskolin. Overall, our findings suggest a possible immunomodulatory effect of TBT, possibly involving cAMP activation.
authors.affiliation: Department of Biology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Nela
authors.initials: N
authors.lastname: Pavlikova
authors.forename: Augustine
authors.initials: A
authors.lastname: Arukwe
mesh_terms: D000818:Animals; D005576:Colforsin / Q000633:toxicity*; D004202:Disinfectants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D007107:Immune System / Q000187:drug effects* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020317:Salmo salar / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D004202:Disinfectants; D016898:Interferon-alpha; D053583:Interleukin-1beta; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014220:Trialkyltin Compounds; D014409:Tumor Necrosis Factor-alpha; D014874:Water Pollutants, Chemical; D016753:Interleukin-10; D005576:Colforsin; C011559:tributyltin; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma